title: Cannabinoids inhibit T-cells via cannabinoid receptor 2 in an in vitro assay for graft rejection, the mixed lymphocyte reaction.
abstract: Cannabinoids are known to have anti-inflammatory and immunomodulatory properties. Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes. This study tested the capacity of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ(9)-THC significantly suppressed the MLR in a dose dependent fashion. The inhibition was via CB2, as suppression could be blocked by pretreatment with a CB2-selective antagonist, but not by a CB1 antagonist, and none of the compounds suppressed the MLR when splenocytes from CB2 deficient mice were used. The CB2 agonists were shown to act directly on T-cells, as exposure of CD3(+) cells to these compounds completely inhibited their action in a reconstituted MLR. Further, the CB2-selective agonists completely inhibited proliferation of purified T-cells activated by anti-CD3 and anti-CD28 antibodies. T-cell function was decreased by the CB2 agonists, as an ELISA of MLR culture supernatants revealed IL-2 release was significantly decreased in the cannabinoid treated cells. Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients.
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, 19140, USA.
authors.forename: Rebecca Hartzell
authors.initials: RH
authors.lastname: Robinson
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Meissler
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Breslow-Deckman
authors.forename: John
authors.initials: J
authors.lastname: Gaughan
authors.forename: Martin W
authors.initials: MW
authors.lastname: Adler
authors.forename: Toby K
authors.initials: TK
authors.lastname: Eisenstein
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D020287:In Situ Nick-End Labeling; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D002186:Cannabinoids; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2